The suprachiasmatic nucleus (SCN) in the anterior hypothalamus contains the major circadian pacemaker in mammals. The purpose of this proposal is to examine how the SCN communicates rhythmic information to its target tissues. The rhythmic neuroendocrine systems that will be investigated are the hypothalamic-pituitary-gonadal and hypothalamic-pituitary- adrenocortical axes. Efferent projections from the SCN to the hypothalamic sites that control these axes have been identified. These projections are known to contain a number of different neurochemicals and the different efferents, as characterized by their neurochemical content, appear to project to selective and specific target areas. Initially, this proposal will test the hypotheses that vasoactive intestinal peptide (VIP) and vasopressin (AVP) are inhibitory signals used by the SCN to time the proestrous surge of LH and the circadian rhythm of glucocorticoid release, respectively. These rhythms are robust and easily measurable and, because the temporal pattern of release of LH and glucocorticoids are so different, examination of both systems should provide more generalizable conclusions about SCN efferent mechanisms. Subsequently, this proposal will test the hypothesis that the inhibitory effects of VIP and AVP are mediated by gamma-aminobutyric acid (GABA). Finally, immunohistochemical studies will determine if VIP and AVP are colocalized with GABA within SCN efferents to the following hypothalamic sites: the medial preoptic nucleus, the paraventricular nucleus, the subparaventricular zone, or the dorsomedial nucleus. This study should contribute to our understanding of the basic mechanisms by which the SCN controls circadian rhythmicity. A better understanding of the principles of SCN efferent functioning may lead to more effective treatments for human disorders in circadian timing.